2'-O-ribose methylation levels of ribosomal RNA distinguish different types of growth arrest in human dermal fibroblasts.

The 2'-O-methylation (2'-O-Me) of ribosomal RNA (rRNA) shows plasticity that is potentially associated with cell phenotypes. We used RiboMeth-seq profiling to reveal growth arrest-specific 2'-O-Me patterns in primary human dermal fibroblasts from three different donors. We exposed cells to hydrogen peroxide to induce cellular senescence and to high cell densities to promote quiescence by contact inhibition. We compared both modes of cell cycle arrest to proliferating cells and could indeed distinguish these conditions by their overall 2'-O-Me patterns. Methylation levels at a small fraction of sites showed plasticity and correlated with the expression of specific small nucleolar RNAs (snoRNAs) but not with expression of fibrillarin. Moreover, we observed subtle senescence-associated alterations in ribosome biogenesis. Knockdown of the snoRNA SNORD87, which acts as a guide for modification of a hypermethylated position in non-proliferating cells, was sufficient to boost cell proliferation. Conversely, depletion of SNORD88A, SNORD88B and SNORD88C, which act as guides for modification of a hypomethylated site, caused decreased proliferation without affecting global protein synthesis or apoptosis. Taken together, our findings provide evidence that rRNA modifications can be used to distinguish and potentially influence specific growth phenotypes of primary cells.

Embedded 3D Bioprinting for Engineering Miniaturized In Vitro Tumor Models.

Embedded extrusion 3D bioprinting is a rapidly emerging additive manufacturing methodology that provides a precise spatial deposition of synthetic or natural-origin low-viscosity bioinks during the extrusion printing process. Such a strategy has to date unlocked the freeform extrusion biofabrication of complex micro-to-macro-scale living architectures for numerous applications, including tissue engineering and in vitro disease modeling. In this chapter, we describe a suspension bioprinting methodology leveraging a continuous viscoelastic biopolymer supporting bath functionalized with divalent calcium cations to enable a rapid processing of user-defined bioinks toward architecturally complex 3D in vitro tumor models. This highly simple and cost-effective viscoelastic supporting bath enables a full freeform biofabrication of cell-laden 3D tumor-mimetic architectures that exhibit structural stability in culture post-printing. The cytocompatibility of the supporting bath, its ease of removal from biofabricated living constructs, and its adaptability for processing different ECM-mimetic bioinks open avenues for multi-scale fabrication of numerous types of physiomimetic 3D tumor models for preclinical screening of candidate therapeutics.

Emotional self-body odors do not influence the access to visual awareness by emotional faces.

A growing body of research suggests that emotional chemosignals in others' body odor (BO), particularly those sampled during fearful states, enhance emotional face perception in conscious and preconscious stages. For instance, emotional faces access visual awareness faster when presented with others' fear BOs. However, the effect of these emotional signals in self-BO, that is, one's own BO, is still neglected in the literature. In the present work, we sought to determine whether emotional self-BOs modify the access to visual awareness of emotional faces. Thirty-eight women underwent a breaking-Continuous Flash Suppression task in which they were asked to detect fearful, happy, and neutral faces, as quickly and accurately as possible, while being exposed to their fear, happiness, and neutral self-BOs. Self-BOs were previously collected and later delivered via an olfactometer, using an event-related design. Results showed a main effect of emotional faces, with happy faces being detected significantly faster than fearful and neutral faces. However, our hypothesis that fear self-BOs would lead to faster emotional face detection was not confirmed, as no effect of emotional self-BOs was found-this was confirmed with Bayesian analysis. Although caution is warranted when interpreting these results, our findings suggest that emotional face perception is not modulated by emotional self-BOs, contrasting with the literature on others' BOs. Further research is needed to understand the role of self-BOs in visual processing and emotion perception.

Extremely giant liver hemangioma: a case beyond the norms.

A 68-year-old overweight woman with no history of oral contraceptive use presented a large liver mass of 40 cm on abdominal ultrasound without associated symptoms. Complete blood count, coagulation study, and liver biochemistry were unremarkable. Abdominal contrast-enhanced CT revealed a 33x24 cm lesion with discontinuous peripheral globular uptake and centripetal fill-in, consistent with an extremely giant hemangioma. It affected all segments of the right lobe, compressing the right suprahepatic vein and displacing all intra-abdominal structures, with a deviation of the midline structures (stomach and pancreas) to the left. Given the hemangioma size and its significant mass effect, surgery was discussed but declined by the patient, who remains asymptomatic 3 years later. Extremely giant liver hemangiomas (>10 cm) are rare, and the approach to asymptomatic patients is debated. Some advocate for prophylactic excision due to the potential for internal bleeding, growth, or rupture, while others suggest intervention for hemangiomas near major vascular structures. The American College of Gastroenterology recommends surgical intervention in such cases, but the European Association for the Study of the Liver suggests a conservative approach for most patients. This case highlights a successful "watch-and-wait" strategy, bringing attention to this unusual condition and its controversial management.

From Temporal Cell Arteritis to Giant Cell Aortitis Presenting as a Constitutional Syndrome: A Case Report.

Giant cell arteritis (GCA) is the most common form of systemic vasculitis in adults, especially in patients over the age of 50. It manifests most commonly with an intense headache and visual symptoms. Although constitutional symptoms are also frequent in GCA, these can be dominant in 15% of patients at first presentation and 20% of patients when relapsing. Treatment with high-dose steroids should be initiated as soon as possible to rapidly control the inflammatory symptoms and prevent ischemic complications, the most feared being blindness from anterior ischemic optic neuropathy. We present a case of a 72-year-old man who presented to the emergency department with a right temporal headache with retroocular radiation associated with scalp hyperesthesia, without any visual symptoms. The patient also reported low-grade fever, night sweats, anorexia, and weight loss over the last two months. The physical exam revealed a tortuous and indurated right superficial temporal artery, which was tender to palpation. The ophthalmological examination was normal. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were elevated, and he also had inflammatory anemia with a hemoglobin of 11.7 g/L. Due to this clinical presentation as well as the elevation of inflammatory markers, the diagnosis of temporal arteritis was suspected, and the patient was started on prednisolone (1 mg/kg). A right temporal artery biopsy was performed on the first week after the initiation of corticotherapy and was negative. After treatment initiation, there was a remission of symptoms accompanied by a decrease and normalization of inflammatory markers. However, after steroid tapering, there was a reappearance of constitutional symptoms but without any other organ-specific symptoms, such as headache, visual loss, arthralgia, or other. The corticosteroid dose was increased to the initial dosage, but there was no improvement in the symptoms this time. After the exclusion of other causes of the constitutional syndrome, a positron-emission tomography (PET) scan was performed, which showed a grade 2 aortitis. The diagnosis of giant cell aortitis was assumed, and given the lack of clinical response to corticotherapy, tocilizumab was initiated with a resolution of constitutional symptoms as well as a normalization of inflammatory markers. In conclusion, we report a case of temporal cell arteritis that further progressed to aortitis manifesting solely with constitutional symptoms. Furthermore, there was no optimal response to corticotherapy and no improvement with tocilizumab, therefore making this a case with a unique and infrequent clinical course. GCA is characterized by a wide variety of symptoms and organ involvement, and although it most frequently affects temporal arteries, it can be associated with aortic involvement that can cause life-threatening structural complications, highlighting the need for a high suspicion index for this condition.

The angry versus happy recognition advantage: the role of emotional and physical properties.

Facial emotional expressions are pivotal for social communication. Their fast and accurate recognition is crucial to promote adaptive responses to social demands, for the development of functional relationships, and for well-being. However, the literature has been inconsistent in showing differentiated recognition patterns for positive vs. negative facial expressions (e.g., happy and angry expressions, respectively), likely due to affective and perceptual factors. Accordingly, the present study explored differences in recognition performance between angry and happy faces, while specifically assessing the role of emotional intensity and global/regional low-level visual features. 98 participants categorized angry and happy faces morphed between neutral and emotional across 9 levels of expression intensity (10-90%). We observed a significantly higher recognition efficiency (higher accuracy and shorter response latencies) for angry compared to happy faces in lower levels of expression intensity, suggesting that our cognitive resources are biased to prioritize the recognition of potentially harmful stimuli, especially when briefly presented at an ambiguous stage of expression. Conversely, an advantage for happy faces was observed from the midpoint of expression intensity, regarding response speed. However, when compensating for the contribution of regional low-level properties of distinct facial key regions, the effect of emotion was maintained only for response accuracy. Altogether, these results shed new light on the processing of facial emotional stimuli, emphasizing the need to consider emotional intensity and regional low-level image properties in emotion recognition analysis.

Differential effect of fisheries to the COVID-19 pandemic in the region of Andalusia (Spain).

Fishing is one of the most widespread and important human activities in coastal ecosystems and it plays a fundamental role in employment and the economy of coastal communities. However, in the period 2020-2021, the global outbreak of COVID-19 negatively affected fishing economic activity. Against this background, Andalusia (South of Spain) is an important region in which the resilience of different fishing exploitation systems can be studied, but within the same social and economic framework. Therefore, the main study aim was to investigate the resilience of fishing activity to the COVID-19 pandemic in two Andalusian fishing grounds (i.e. Atlantic and Mediterranean). We analysed daily landings and the first-sale prices of fresh fish of the most caught species in both fishing grounds, while taking into account the different seasonal behaviour of the fisheries. Generalised Linear Models were used to compare the data, which were obtained during periods in which the COVID-19 severity levels differed. These levels were implemented according to political measures. The final objective was to understand how the degree of industrialisation in the fleets can hinder or help maintain the economic activity of fisheries during major crises.

Advances in bioengineering pancreatic tumor-stroma physiomimetic Biomodels.

Pancreatic cancer exhibits a unique bioarchitecture and desmoplastic cancer-stoma interplay that governs disease progression, multi-resistance, and metastasis. Emulating the biological features and microenvironment heterogeneity of pancreatic cancer stroma in vitro is remarkably complex, yet highly desirable for advancing the discovery of innovative therapeutics. Diverse bioengineering approaches exploiting patient-derived organoids, cancer-on-a-chip platforms, and 3D bioprinted living constructs have been rapidly emerging in an endeavor to seamlessly recapitulate major tumor-stroma biodynamic interactions in a preclinical setting. Gathering on this, herein we showcase and discuss the most recent advances in bio-assembling pancreatic tumor-stroma models that mimic key disease hallmarks and its desmoplastic biosignature. A reverse engineering perspective of pancreatic tumor-stroma key elementary units is also provided and complemented by a detailed description of biodesign guidelines that are to be considered for improving 3D models physiomimetic features. This overview provides valuable examples and starting guidelines for researchers envisioning to engineer and characterize stroma-rich biomimetic tumor models. All in all, leveraging advanced bioengineering tools for capturing stromal heterogeneity and dynamics, opens new avenues toward generating more predictive and patient-personalized organotypic 3D in vitro platforms for screening transformative therapeutics targeting the tumor-stroma interplay.

Programmable Living Units for Emulating Pancreatic Tumor-Stroma Interplay.

Bioengineering close-to-native in vitro models that emulate tumors bioarchitecture and microenvironment is highly appreciable for improving disease modeling toolboxes. Herein, pancreatic cancer living units-so termed cancer-on-a-bead models-are generated. Such user-programmable in vitro platforms exhibit biomimetic multicompartmentalization and tunable integration of cancer associated stromal elements. These stratified units can be rapidly assembled in-air, exhibit reproducible morphological features, tunable size, and recapitulate spatially resolved tumor-stroma extracellular matrix (ECM) niches. Compartmentalization of pancreatic cancer and stromal cells in well-defined ECM microenvironments stimulates the secretion of key biomolecular effectors including transforming growth factor ß and Interleukin 1-ß, closely emulating the signatures of human pancreatic tumors. Cancer-on-a-bead models also display increased drug resistance to chemotherapeutics when compared to their reductionistic counterparts, reinforcing the importance to differentially model ECM components inclusion and their spatial stratification as observed in vivo. Beyond providing a universal technology that enables spatial modularity in tumor-stroma elements bioengineering, a scalable, in-air fabrication of ECM-tunable 3D platforms that can be leveraged for recapitulating differential matrix composition occurring in other human neoplasias is provided here.

Equalden.HD: An R Package for testing the equality of a high dimensional set of densities.

BACKGROUND AND OBJECTIVE: Nowadays the "low sample size, large dimension" scenario is often encountered in genetics and in the omic sciences, where the microarray data is typically formed by a large number of possibly dependent small samples. Standard methods to solve the k-sample problem in such a setting are of limited applicability due to lack of theoretical validation for large k, lengthy computational times, missing software solutions, or inability to deal with statistical dependence among the samples. This paper presents the R package Equalden.HD to overcome the referred limitations. METHODS: The package implements several tests for the null hypothesis that a large number of samples follow a common density. These methods are particularly well suited to the "low sample size, large dimension" setting. The implemented procedures allow for dependent samples. For each method Equalden.HD reports, among other things, the standardized value of the test statistic and the corresponding p-value. The package also includes two high-dimensional genetic data sets, Hedenfalk and Rat, which are used in this paper for illustration purposes. RESULTS: The usage of Equalden.HD has been illustrated through the analysis of Hedenfalk and Rat genetic data. Statistical dependence among the samples was found for both genetic data sets. The application of an appropriate k-sample test within Equalden.HD rejected the null hypothesis of inter-samples homogeneity. The methods were used to test for the within groups homogeneity in cluster analysis too, which is usually performed when the k samples are found to be significantly different. Equalden.HD helped to identify the individuals which are responsible for the lack of homogeneity of the samples. The limitations of the standard Kruskal-Wallis test for the identification of homogeneous clusters have been highlighted. CONCLUSIONS: The methods implemented by Equalden.HD are the unique omnibus nonparametric k-sample tests that have been validated as k grows. Furthermore, the package provides suitable corrections for possibly dependent samples, which is another distinctive feature. Thus, the package opens new doors for the statistical analysis of omic data. Limitations of standard methods (e.g. Anderson-Darling and Kruskal-Wallis) and existing software solutions in the setting with a large k have been emphasized.

Progressive Multifocal Leukoencephalopathy Associated With Idiopathic CD8+ Lymphocytopenia.

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system (CNS) caused by the polyoma John Cunningham (JC) virus. This virus is rarely pathogenic in immunocompetent individuals, being associated with profound cellular immunosuppression. We present a case of a 72-year-old woman with schizoaffective disorder who presented to the emergency department with dysarthria and right hemiataxia. The initial computer tomography was normal and the diagnosis of ischemic stroke was first assumed. However, during hospitalization there was a progressive worsening of symptoms with cerebellar ataxia, and the magnetic resonance revealed a lesion in the right middle cerebellar peduncle hypointense in T1 and hyperintense on T2/fluid attenuated inversion recovery (FLAIR) sequence, suggestive of PML. Although the first cerebrospinal fluid analysis was negative, the second one was positive for the JC virus. Furthermore, due to radiological and clinical progression, mirtazapine was started and the patient underwent a course of intravenous immunoglobulin, with no response. In parallel, causes of immunosuppression were investigated, which led to the diagnosis of idiopathic CD8+ lymphocytopenia. Due to rapid progression of symptoms and radiological worsening of lesions, pembrolizumab was administered. After the first administration of pembrolizumab there was a transitory clinical stabilization. However, shortly after the second administration of pembrolizumab, the patient developed stridor with bilateral vocal cord paralysis and subsequent symptom progression, which led to the death of the patient three months after the appearance of initial symptoms. In conclusion, we report a case of a PML in a patient with idiopathic CD8+ lymphocytopenia, enhancing the need for a high suspicion index for this entity as well as for occult and less frequent forms of immunosuppression. Although there have been various case reports of favourable outcomes with pembrolizumab for PML, more research is needed, particularly to identify patient factors that might be associated with better responses to this therapy.

Acute variceal bleeding and out-of-hours endoscopy: Evaluation of an emergency care setting according to Baveno VI guidelines adherence.

BACKGROUND: The extent to which patients with acute variceal bleeding (AVB) receive recommended care is largely unknown. AIM: to evaluate the adherence of the 4 major Baveno VI recommendations [vasoactive agents, prophylactic antibiotic, esophagogastroduodenoscopy (EGD) within 12 hours, endoscopic variceal ligation (EVL)] as a marker of quality of an emergency model. METHODS: Retrospective evaluation of AVB admissions to a tertiary centre in which endoscopy was available 24hours-a-day, with a regional out-of-hours service at night (the furthest hospital is 200Km away). Patients were divided in directly admitted or transferred from other centres. RESULTS: 210 AVB patients were included; 101 (48.1%) were directly admitted. The majority of patients were submitted to vasoactive agents (85.7%) and prophylactic antibiotics (79%) before EGD. In 178 patients (84.8%) endoscopy was performed within 12h and EVL was the procedure of choice in 116 (74.8%) (only oesophageal varices). No significant differences were observed between directly admitted and transferred patients in adherence rates. Overall rebleeding rate was 8.6%, in-hospital mortality 11.4% and 6-week mortality 20%. CONCLUSION: Adherence to quality metrics was high which might have played a vital role for reported outcomes. These results suggest that this model of care, provides accessibility and equity in access to urgent endoscopy.

Impact of Liver Test Abnormalities and Chronic Liver Disease on the Clinical Outcomes of Patients Hospitalized with COVID-19.

BACKGROUND AND AIMS: The impact of SARS-CoV-2 infection on the liver and the possibility of chronic liver disease (CLD) as a risk factor for COVID-19 severity is not fully understood. Our goal was to describe clinical outcomes of COVID-19 inpatients regarding the presence of abnormal liver tests and CLD. METHODS: A retrospective analysis of patients with SARS-CoV-2 infection, hospitalized in a tertiary center in Portugal, was performed. Studied outcomes were disease and hospitalization length, COVID-19 severity, admission to intensive care unit (ICU) and mortality, analyzed by the presence of abnormal liver tests and CLD. RESULTS: We included 317 inpatients with a mean age of 70.4 years, 50.5% males. COVID-19 severity was moderate to severe in 57.4% and critical in 12.9%. The mean disease length was 37.8 days, the median hospitalization duration 10.0 days and overall mortality 22.8%. At admission, 50.3% showed abnormal liver tests, and 41.5% showed elevated aminotransferase levels, from which 75.4% were mild. Elevated aminotransferase levels at admission were associated with COVID-19 severity (78.7 vs. 63.3%, p = 0.01), ICU admission (13.1 vs. 5.92%, p = 0.034) and increased mortality (25.8 vs. 13.3%, p = 0.007). However, in a subgroup analysis, only aspartate transaminase (AST) was associated with these worse outcomes. Alkaline phosphatase was elevated in 11.4% of the patients and was associated with critical COVID-19 (21.1 vs. 9.92%, p = 0.044) and mortality (20.4 vs. 9.52%, p = 0.025), while 24.6% of the patients showed elevated γ-glutamyl transferase, which was associated with ICU admission (42.3 vs. 22.8%, p = 0.028). Fourteen patients had baseline CLD (4.42%), 3 with liver cirrhosis. Alcohol (n = 6) and nonalcoholic fatty liver disease (n = 6) were the most frequent etiologies. CLD patients had critical COVID-19 in 21.4% (p = 0.237), mean disease length of 36.6 days (p = 0.291), median hospitalization duration of 11.5 days (p = 0.447) and a mortality rate of 28.6% (p = 0.595), which increased to 66.7% among cirrhotic patients (p = 0.176). CONCLUSIONS: Liver test abnormalities in COVID-19 patients were frequent but most commonly mild. AST, but not alanine transaminase, was associated with worse clinical outcomes, such as COVID-19 severity and mortality, probably indicating these outcomes were independent of liver injury. A low prevalence of CLD was seen, and a clear impact on COVID-19 outcomes was not seen.

Long-Term Follow-Up of a Portuguese Single-Centre Cohort of Persons with Haemophilia and Hepatitis C Virus Infection.

INTRODUCTION: Persons with haemophilia (PWH) used to represent a population with a high prevalence of hepatitis C virus (HCV) infection due to the use of contaminated blood products. Although the goals of antiviral therapy are the same as the general population, long real-life follow-up data regarding their outcomes are still scarce. Our aim was to report the outcomes of HCV infection and the results of antiviral therapy in PWH. METHODS: A retrospective analysis was performed in a single-centre cohort of PWH with positive HCV antibody. Outcomes registered were rate of spontaneous clearance of HCV, sustained virologic response (SVR) achievement, development of end-stage liver disease, and all-cause and liver-related mortality. RESULTS: Out of 131 PWH, 73 (55.7%) had positive HCV antibody. During a median follow-up time of 22 years, 46 patients (63.9%) developed chronic hepatitis C, of which 16 (34.8%) developed cirrhosis. Treatment was pursued in 34 PWH. Most (n = 32) were first treated with interferon (IFN)-based regimens with SVR rates of 40.6%. Direct-acting antivirals were used in 14 IFN-experienced and 2 naïve patients, with an overall SVR rate of 100%. Overall, 17 patients (23.3%) died during the follow-up, only 4 related to liver disease. Of these, none had achieved SVR. CONCLUSIONS: We describe the outcomes of a cohort of Portuguese PWH and hepatitis C exposure after two decades of follow-up, with a lower mortality than previously described. Our response rates to HCV treatment were comparable to those in the general population and stress the importance of early treatment.

INTRODUÇÃO: A população de doentes com hemofilia (DCH) representa uma população com alta prevalência de infeção pelo virus da hepatite C (VHC), atendendo à utilização passada de derivados sanguíneos contaminados. Apesar de os objetivos terapêuticos nesta população serem semelhantes aos da população geral, estudos de vida real com follow-up de longa data são ainda escassos. O nosso objetivo consistiu em avaliar os outcomes infeção VHC, bem como, os resultados da terapéutica antivírica nos DCH. MÉTODOS: Foi avaliada retrospetivamente uma coorte unicêntrica de DCH com positividade para anti-VHC. Os outcomes registados foram a ocorrência de clearance espontêneo, resposta virológica sustentada (RVS), desenvolvimento de doença hepática terminal e mortalidade. RESULTADOS: De 131 DCH, 73 (55.7%) apresentavam positividade para o anticorpo VHC. Durante um follow-up médio de 22 anos, 46 doentes (63.9%) desenvolveram hepatite crónica C, 16 (34.8%) dos quais com desenvolvimento de cirrose. Trinta e quatro DCH foram tratados, a maioria (n = 32) exposta previamente a regimes baseados no interferão (IFN) com RVS de 40.6%. Antivíricos de ação direta foram utilizados em 14 doentes experimentados a IFN e 2 naïves com uma taxa de RVS geral de 100%. Morte foi observada em 17 doentes (23.3%), apenas 4 relacionadas à doença hepática. Destes nenhum tinha atingido RVS. CONCLUSÕES: Descrevemos os outcomes de uma coorte portuguesa de DCH e VHC após duas décadas de follow-up, mostrando uma mortalidade inferior à previamente descrita. As taxas de RVS mostradas foram comparáveis com as da população geral salientando a importancia do tratamento precoce.

Canopy structure and morphogenesis of Italian ryegrass intercropped with red clover under cutting intervals determined by thermal sum / Estrutura do dossel e morfogênese do azevém anual consorciado com trevo vermelho em intervalos de corte determinados por soma térmica

ABSTRACT: The canopy structure and morphogenesis of ryegrass (Lolium multiflorum Lam.) was investigated after it was over seeded with Tifton 85 (Cynodon spp.) and intercropped with red clover (Trifolium pratense L.). Time intervals between cuts were determined by different thermal sums (125, 250, 375, and 500 degree-days [DD]). Cuts were conducted at a height equivalent to 50% of the average canopy height. Morphogenic and structural data were collected from July to October of 2016 and 2017, from a completely randomized block experimental design. Canopy height, extended tiller height, pseudostem length, and forage mass were fitted to linear equations according to the thermal sums. Interaction of ryegrass with red clover was the highest (12.1%) for longer cut intervals (375 and 500 DD). The leaf appearance rate (0.0080 leaf/DD), phyllochron value (128.8 DD), and senescence rate (0.10 cm/DD) of ryegrass were comparable between the different intervals. The slowest elongation rate (0.06 cm/DD) with the shortest interval duration between cuts (171.6 DD) was observed in the 125 DD interval. According to the findings from this 2-year experiment, the use of a 250 DD cut interval was recommended between grazing events, taking into account the efficiency of forage use, ryegrass leaf, stem ratio, and interactions with red clover in the canopy under rotational stocking.

RESUMO: A estrutura do dossel e a morfogênese do azevém (Lolium multiflorum Lam.) foram investigadas após a sobressemeadura em Tifton 85 (Cynodon spp.) e consorciado com trevo vermelho (Trifolium pratense L.). Os intervalos de tempo entre os cortes foram determinados por diferentes somas térmicas (125, 250, 375 e 500 graus-dia [GD]). Os cortes foram realizados a uma altura equivalente a 50% da altura média do dossel. Os dados morfogênicos e estruturais foram coletados no período de julho a outubro de 2016 e 2017, em um delineamento experimental de blocos ao acaso. A altura do dossel, a altura estendida do perfilho, o comprimento do pseudocolmo e a massa de forragem se ajustaram a equações lineares de acordo com a soma térmica. A consorciação de azevém e trevo vermelho foi maior (12,1%) para intervalos de corte mais longos (375 e 500 GD). A taxa de aparecimento foliar (0,0080 folha/GD), filocrono (128,8 GD) e a taxa de senescência (0,10 cm /GD) do azevém não foram diferentes entre os intervalos de corte. A menor taxa de elongação (0,06 cm/GD) e duração de elongação (171,6 GD) foi observada no menor intervalo entre cortes, 125 GD. De acordo com os achados deste experimento de dois anos, recomenda-se o uso de um intervalo de corte de 250 GD entre os eventos de pastejo, levando em consideração a eficiência do uso de forragem, proporção de folhas e colmo de azevém e trevo vermelho no dossel, sob lotação rotativa.

Treating Untreatable Rectal Varices.

BACKGROUND: Rectal varices are portosystemic collaterals that arise as a complication of portal hypertension. Despite their significant prevalence among cirrhotic patients, clinically important bleeding occurs only in a minority. Various treatment options are available, with endoscopic therapies being widely used, and both interventional radiology and surgery being considered for refractory bleeding rectal varices. CASE: We report the case of a 61-year-old male with hepatic cirrhosis and bleedingrectal varices refractory to endoscopic therapy, successfully managed with a combination of transjugular intrahepatic portosystemic shunt (TIPS) and selective variceal embolization. CONCLUSIONS: Radiological techniques are effective options for refractory bleeding. Adding embolization to TIPS implantation could represent a valid adjunctive measure for haemostasis of recurrent rectal variceal bleeding.

Management of Gastrointestinal Toxicity from Immune Checkpoint Inhibitor.

Immune checkpoint inhibitors have shown anti-tumour activity in cancers such as melanoma, renal cell carcinoma, non-small-cell lung cancer, urothelial carcinoma, colorectal cancer, and Hodgkin's lymphoma. Though immune checkpoint inhibitors have revolutionized the treatment and prognosis of some advanced malignancies, they are also associated with a significant risk of immune-related adverse events. These adverse events can occur in any organ system, but gastrointestinal side effects are among the most commonly reported, with manifestations ranging from mild diarrhoea to severe colitis, sharing some features with inflammatory bowel disease. Anticipating a greater use of these drugs in the future, gastroenterologists should expect to be increasingly faced with gastrointestinal immune-related adverse events. Knowledge of these toxicities, as well as effective management algorithms, is essential to enable early diagnosis and treatment, decreasing morbidity and mortality. We reviewed the currently available literature on gastrointestinal toxicity induced by immune checkpoint inhibitors, namely the clinical features, diagnosis, and management.

Os inibidores dos checkpoint imunológicos demonstraram atividade antitumoral em neoplasias como o melanoma, o carcinoma de células renais, o carcinoma pulmonar de não pequenas células, o carcinoma urotelial, o carcinoma colorretal e o linfoma de Hodgkin. Estes fármacos, embora tenham revolucionado o tratamento e o prognóstico de algumas neoplasias avançadas, também se associam a um risco considerável de efeitos adversos associadosao sistema imunitário. Qualquer órgão pode ser afetado, mas os efeitos adversos gastrointestinais estão entre os mais comumente relatados. As manifestações gastrointestinais variam desde diarreia ligeira a colite grave, a qual pode evidenciar características idênticas às da doença inflamatória intestinal. Antecipando uma maior utilização destes fármacos no futuro, os gastroenterologistas devem esperar confrontar-se cada vez mais com este tipo de efeitos adversos. O conhecimento dessas toxicidades, bem como dos algoritmos de abordagem destes doentes é fundamental para um diagnóstico e tratamento precoces, diminuindo desta forma a morbilidade e a mortalidade. Os autores pretenderam rever a literatura mais atual sobre a toxicidade gastrointestinal induzida pelos inibidores dos checkpoint imunológicos, nomeadamente apresentação clínica, abordagem diagnóstica e terapêutica.

The scent of the other women: Body odor-induced behavioral and physiological effects on face categorization.

In body odor research, the interaction of female donors and receivers is scarcely investigated. With the aim to investigate effects of female body odor in a competitive context, we tested 51 women divided into two groups (i.e., a competitive and a non-competitive group, based on verbal instructions). Between groups, we explored whether female body odor exposure (vs. masker odor) modulates emotion categorization (via RT variance and distribution) and physiological reactions (via instantaneous heart rate) in a task with dynamic male and female faces as either angry or happy. Women in the competitive group reported to feel more competitive and performed more accurately. They gathered more emotional information to categorize dynamic faces and when additionally exposed to female body odor, they showed a resistance to cardiac deceleration. Lapses of attention (via RT distribution) occurred irrespective of body odor exposure. Our results support the idea that female body odors, presented in a competitive context, contrast cardiac deceleration and, by tendency, modulate emotion categorization. Data are discussed in the context of chemosignaling and social interactions among women.